CHARACTERIZATION OF CARDIAC ANGIOTENSIN CONVERTING ENZYME (ACE) AND INVIVO INHIBITION FOLLOWING ORAL QUINAPRIL TO RATS

1 Angiotensin converting enzyme (ACE) from the rat heart and lung was studied by use of the radioligand [125I]-351A. 2. Displacement of the bound radioinhibitor [125I]-351A was used to assess the relative potency of six ACE inhibitors in rat heart and lung homogenates and estimate the binding association constant (K(A)). 3. The K(A) for atrial preparations was significantly higher than that of the lung (P < 0.025) and also the ventricles (P < 0.005). Ventricular preparations and preparations from the lung also differed significantly (P < 0.05). These differences in K(A) were noted for all six ACE inhibitors used to displace the radioligand. 4. The rank order of potency of the ACE inhibitors was quinaprilat = benazeprilat > perindoprilat > 351A > lisinopril > fosinoprilat. 5. Cardiac ACE inhibition was studied ex vivo following oral administration of quinapril to rats. Following 0.3 mg kg-1 quinapril, the time course and degree of inhibition of ventricular and atrial ACE were similar. 6. These results suggest that the detected differences in K(A) noted have only a limited potential biological significance. The difference in K(A) may reflect variations in the structure or conformation of ACE in different tissues.